To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective. An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used. After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (beta:a,not sign-32; 95 %CI: -54 to -10) and healthcare costs (beta:a,not sign-126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (beta:a,not sign186; 95 %CI:19-557). Societal costs did not significantly differ between groups (beta:a,not sign-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (a parts per thousand currency sign0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness. From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand. ClinicalTrials.gov Identifier: NCT00713843.